[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Home::
Journal Information::
Articles archive::
Publication Ethics::
Peer Review Process::
Indexing Databases::
For Authors::
For Reviewers::
Subscription::
Contact us::
Site Facilities::
::
Google Scholar Metrics

Citation Indices from GS

AllSince 2019
Citations67323963
h-index2721
i10-index20195

..
Search in website

Advanced Search
..
Receive site information
Enter your Email in the following box to receive the site news and information.
..
Registered in

AWT IMAGE

AWT IMAGE

..
:: Volume 32, Issue 3 (8-2024) ::
Journal of Ilam University of Medical Sciences 2024, 32(3): 111-122 Back to browse issues page
Drug repurposing for breast cancer treatment using bioinformatics approach
Habib MotieGhader *
Dept of Biology, Tabriz Branch, Islamic Azad University, Tabriz, Iran , habib_moti@iaut.ac.ir
Abstract:   (224 Views)
Introduction:  Breast cancer, which is one of the most common cancers with high mortality in women, has always been the focus of researchers, and every day, scientists are trying to identify mechanisms, genes, and medicines related to this disease. Nowadays, bioinformatics methods are used to identify and repurpose drugs for the treatment of diseases, especially cancer.
Material & Methods: In this study, bioinformatics and biological network analysis were used to identify candidate drugs for breast cancer treatment. In this regard, analysis of the protein interaction network and drug-gene network were employed. The needed data were collected from the GEO database with the access code GSE54002. For the selected data set, genes with significant expression changes between two groups of healthy people and people with breast cancer cases were selected and considered primary genes. Thereafter, the protein-protein interaction network was constructed using the STRING database, and a significant gene module was obtained from the network. Following that, gene ontology studies and biological pathways were conducted. Next, the drug-gene network was constructed to identify drugs that target module genes and were introduced as essential drugs for the treatment of breast cancer. Cytoscape software and STRING and OncoDB databases were used to reconstruct and analyze the networks.
Results: After analyzing the protein-protein interaction network and the drug-gene network, three important drugs that target the genes of the modules were identified and introduced as candidate drugs for the treatment of breast cancer. These drugs were RG-1530, R-406, and GW441756x.
Discussion & Conclusion: The obtained results demonstrated that the introduced drugs (RG-1530, R-406, and GW441756x) can be effective in the treatment of breast cancer
Keywords: Bioinformatics, Breast cancer, Drug-gene network, Protein-protein interaction network
Full-Text [PDF 1413 kb]   (204 Downloads)    
Type of Study: Research | Subject: biotechnolohgy
Received: 2024/01/4 | Accepted: 2024/05/20 | Published: 2024/08/5
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;682:394-424. doi: 10.3322/caac.21492.
2. Harbeck N, Gnant M. Breast cancer. Lancet 2017;389:1134-50. doi: 10.1016/S0140-6736(16)31891-8.
3. Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Primers 2019;5:66. doi: 10.1038/s41572-019-0111-2.
4. Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY, et al. Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med 2014;6:1279-93. doi: 10.15252/emmm.201404208.
5. Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, et al. STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res 2009;37:D412-6. doi: 10.1093/nar/gkn760.
6. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498-504. doi: 10.1101/gr.1239303.
7. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 2017;45:W98-W102. doi: 10.1093/nar/gkx247.
8. Kolinsky K, Tovar C, Zhang YE, Railkar A, Yang H, Carvajal D, et al. Preclinical evaluation of the novel multi-targeted agent R1530. Cancer Chemother Pharmacol 2011;68:1585-94. doi: 10.1007/s00280-011-1608-x.
9. Khasraw M, Bell R, Dang C. Epirubicin: is it like doxorubicin in breast cancer? A clinical review. Breast 2012;21:142-9. doi: 10.1016/j.breast.2011.12.012.
10. Das T, Nandy S, Pandey KD, Al-Tawaha AR, Swamy MK, Kumar V, et al. 12 - An update on paclitaxel treatment in breast cancer. Paclitaxel 2022; 287-308. doi: 10.1016/B978-0-323-90951-8.00013-8.
11. Jordan VC. The role of tamoxifen in the treatment and prevention of breast cancer. Curr Probl Cancer 1992;16:129-76. doi: 10.1016/0147-0272(92)90002-6.
12. Shariati M, Meric-Bernstam F. Targeting AKT for cancer therapy. Expert Opin Investig Drugs 2019;28:977-88. doi: 10.1080/13543784.2019.1676726.
13. Novais P, Silva PMA, Amorim I, Bousbaa H. Second-Generation Antimitotics in Cancer Clinical Trials. Pharmaceutics 2021;13:1011. doi: 10.3390/pharmaceutics13071011.
14. Katayama R, Khan TM, Benes C, Lifshits E, Ebi H, Rivera VM, et al. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A 2011;108:7535-40. doi: 10.1073/pnas.1019559108.
15. Wang J, Wang JQ, Cai CY, Cui Q, Yang Y, Wu ZX, et al. Reversal Effect of ALK Inhibitor NVP-TAE684 on ABCG2-Overexpressing Cancer Cells. Front Oncol 2020;10:228. doi: 10.3389/fonc.2020.00228.
16. Jemaà M, Vitale I, Kepp O, Berardinelli F, Galluzzi L, Senovilla L, et al. Selective killing of p53-deficient cancer cells by SP600125. EMBO Mol Med 2012;4:500-14. doi: 10.1002/emmm.201200228.
17. Kim JH, Chae M, Choi AR, Sik Kim H, Yoon S. SP600125 overcomes antimitotic drug-resistance in cancer cells by increasing apoptosis with independence of P-gp inhibition. Eur J Pharmacol 2014;723:141-7. doi: 10.1016/j.ejphar.2013.11.026.
18. Kim JH, Kim TH, Kang HS, Ro J, Kim HS, Yoon S. SP600125, an inhibitor of Jnk pathway, reduces viability of relatively resistant cancer cells to doxorubicin. Biochem Biophys Res Commun 2009;387:450-5. doi: 10.1016/j.bbrc.2009.07.036.
19. Aftab A, Shahzad S, Hussain HMJ, Khan R, Irum S, Tabassum S. CDKN2A/P16INK4A variants association with breast cancer and them in-silico analysis. Breast Cancer 2019;26:11-28. doi: 10.1007/s12282-018-0894-0.
20. Ma YZ, Tang ZB, Sang CY, Qi ZY, Hui L, Chen SW. Synthesis and biological evaluation of nitroxide labeled pyrimidines as Aurora kinase inhibitors. Bioorg Med Chem Lett 2019;29:694-99. doi: 10.1016/j.bmcl.2019.01.034.
21. Liu M, Li Y, Zhang C, Zhang Q. Role of aurora kinase B in regulating resistance to paclitaxel in breast cancer cells. Hum Cell 2022;35:678-93. doi: 10.1007/s13577-022-00675-8.
22. Arbitrario JP, Belmont BJ, Evanchik MJ, Flanagan WM, Fucini RV, Hansen SK, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol 2010;65:707-17. doi: 10.1007/s00280-009-1076-8.
23. Baldini E, Tuccilli C, Prinzi N, Sorrenti S, Antonelli A, Gnessi L, et al. Effects of selective inhibitors of Aurora kinases on anaplastic thyroid carcinoma cell lines. Endocrine-Related Cancer 2014;21:797-811.doi: 10.1530/ERC-14-0299.
24. Infante JR, Camidge DR, Mileshkin LR, Chen EX, Hicks RJ, Rischin D, et al. Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors. J Clin Oncol 2012;30:1527-33. doi: 10.1200/JCO.2011.38.9346.
25. Kitabayashi T, Dong Y, Furuta T, Sabit H, Jiapaer S, Zhang J, et al. Identification of GSK3β inhibitor kenpaullone as a temozolomide enhancer against glioblastoma. Sci Rep 2019;9:10049. doi: 10.1038/s41598-019-46454-8.
26. Sun S, Xue D, Chen Z, Ou-Yang Y, Zhang J, Mai J, et al. R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells. Cell Death Dis 2019;10:358. doi: 10.1038/s41419-019-1587-0.
27. Duran GE, Sikic BI. The Syk inhibitor R406 is a modulator of P-glycoprotein (ABCB1)-mediated multidrug resistance. PLoS One 2019;14:e0210879. doi: 10.1371/journal.pone.0210879.
28. Ghotra VP, He S, van der Horst G, Nijhoff S, de Bont H, Lekkerkerker A, et al. SYK is a candidate kinase target for the treatment of advanced prostate cancer. Cancer Res 2015;75:230-40. doi: 10.1158/0008-5472.CAN-14-0629.
29. Lage-Rupprecht V, Schultz B, Dick J, Namysl M, Zaliani A, Gebel S, et al. A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism. Patterns 2022;3:100433. doi: 10.1016/j.patter.2021.100433.
30. Elkins JM, Fedele V, Szklarz M, Abdul Azeez KR, Salah E, Mikolajczyk J, et al. Comprehensive characterization of the Published Kinase Inhibitor Set. Nat Biotechnol 2016;34:95-103. doi: 10.1038/nbt.3374.
31. Liu JJ, Higgins B, Ju G, Kolinsky K, Luk KC, Packman K, et al. Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors. ACS Med Chem Lett 2013;4:259-63. doi: 10.1021/ml300351e.
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA


XML   Persian Abstract   Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

MotieGhader H. Drug repurposing for breast cancer treatment using bioinformatics approach. J. Ilam Uni. Med. Sci. 2024; 32 (3) :111-122
URL: http://sjimu.medilam.ac.ir/article-1-8199-en.html


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 32, Issue 3 (8-2024) Back to browse issues page
مجله دانشگاه علوم پزشکی ایلام Journal of Ilam University of Medical Sciences
Persian site map - English site map - Created in 0.16 seconds with 41 queries by YEKTAWEB 4657